Abstract
Cognitive impairment is a common symptom in individuals with Multiple Sclerosis (MS), but meaningful, reliable biomarkers relating to cognitive decline have been elusive, making evaluation of the impact of therapeutics on cognitive function difficult. Here, we combine pathway-based MRI measures of structural and functional connectivity to construct a metric of functional decline in MS. The Structural and Functional Connectivity Index (SFCI) is proposed as a simple, z-scored metric of structural and functional connectivity, where changes in the metric have a simple statistical interpretation and may be suitable for use in clinical trials. Using data collected at six time points from a 2-year longitudinal study of 20 participants with MS and 9 age- and sex-matched healthy controls, we probe two common symptomatic domains, motor and cognitive function, by measuring structural and functional connectivity in the transcallosal motor pathway and posterior cingulum bundle. The SFCI is significantly lower in participants with MS compared to controls (p = 0.009) and shows a significant decrease over time in MS (p = 0.012). The change in SFCI over two years performed favorably compared to measures of brain parenchymal fraction and lesion volume, relating to follow-up measures of processing speed (r = 0.60, p = 0.005), verbal fluency (r = 0.57, p = 0.009), and score on the Multiple Sclerosis Functional Composite (r = 0.67, p = 0.003). These initial results show that the SFCI is a suitable metric for longitudinal evaluation of functional decline in MS.
Highlights
Physical disability and upper extremity function are hallmark symptoms of Multiple Sclerosis (MS), and are among the most important factors affecting quality of life [1, 2]
Given the frequency of memory impairment in MS [3, 14], we subsequently extended our study of diffusion tensor imaging (DTI)- and resting state functional magnetic resonance imaging (rsfMRI)-based connectivity to the posterior cingulum bundle, a pathway connecting the antero-mesial temporal lobe (AMTL) and the posterior cingulate cortex (PCC) and subserving episodic memory [15]
The third time point was removed for a different participant with MS, because technical difficulties prevented the acquisition of DTI data at that visit
Summary
Physical disability and upper extremity function are hallmark symptoms of Multiple Sclerosis (MS), and are among the most important factors affecting quality of life [1, 2]. Another common symptom is cognitive dysfunction, affecting approximately 40% to 65% of patients and impacting employment, daily living skills, and overall quality of life [3,4,5,6]. Treatment efficacy is often judged by impact on progression of motor disability [7], with less focus on cognitive.
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